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Benzimidazole-Triazole Hybrids as Antimicrobial and Antiviral Agents: A Systematic Review
Antibiotics ( IF 0 ) Pub Date : 2023-07-22 , DOI: 10.3390/antibiotics12071220
MariaMarinescu
Bacterial infections have attracted the attention of researchers in recent decades, especially due to the special problems they have faced, such as their increasing diversity and resistance to antibiotic treatment. The emergence and development of the SARS-CoV-2 infection stimulated even more research to find new structures with antimicrobial and antiviral properties. Among the heterocyclic compounds with remarkable therapeutic properties, benzimidazoles, and triazoles stand out, possessing antimicrobial, antiviral, antitumor, anti-Alzheimer, anti-inflammatory, analgesic, antidiabetic, or anti-ulcer activities. In addition, the literature of the last decade reports benzimidazole-triazole hybrids with improved biological properties compared to the properties of simple mono-heterocyclic compounds. This review aims to provide an update on the synthesis methods of these hybrids, along with their antimicrobial and antiviral activities, as well as the structure–activity relationship reported in the literature. It was found that the presence of certain groups grafted onto the benzimidazole and/or triazole nuclei (-F, -Cl, -Br, -CF3, -NO2, -CN, -CHO, -OH, OCH3, COOCH3), as well as the presence of some heterocycles (pyridine, pyrimidine, thiazole, indole, isoxazole, thiadiazole, coumarin) increases the antimicrobial activity of benzimidazole-triazole hybrids. Also, the presence of the oxygen or sulfur atom in the bridge connecting the benzimidazole and triazole rings generally increases the antimicrobial activity of the hybrids. The literature mentions only benzimidazole-1,2,3-triazole hybrids with antiviral properties. Both for antimicrobial and antiviral hybrids, the presence of an additional triazole ring increases their biological activity, which is in agreement with the three-dimensional binding mode of compounds. This review summarizes the advances of benzimidazole triazole derivatives as potential antimicrobial and antiviral agents covering articles published from 2000 to 2023.
Combination Therapy with Ciprofloxacin and Pentamidine against Multidrug-Resistant Pseudomonas aeruginosa: Assessment of In Vitro and In Vivo Efficacy and the Role of Resistance–Nodulation–Division (RND) Efflux Pumps
Antibiotics ( IF 0 ) Pub Date : 2023-07-26 , DOI: 10.3390/antibiotics12081236
MeganFletcher,AlexMcCormack,BenjaminJ.Parcell,PeterJ.Coote
The aim of this work was to (i) evaluate the efficacy of a combination treatment of pentamidine with ciprofloxacin against Galleria mellonella larvae infected with an MDR strain of P. aeruginosa and (ii) determine if pentamidine acts as an efflux-pump inhibitor. Resistant clinical isolates, mutant strains overexpressing one of three RND efflux pumps (MexAB-OprM, MexCD-OprJ, and MexEF-OprN), and a strain with the same three pumps deleted were used. MIC assays confirmed that the clinical isolates and the mutants overexpressing efflux pumps were resistant to ciprofloxacin and pentamidine. The deletion of the three efflux pumps induced sensitivity to both compounds. Exposure to pentamidine and ciprofloxacin in combination resulted in the synergistic inhibition of all resistant strains in vitro, but no synergy was observed versus the efflux-pump deletion strain. The treatment of infected G. mellonella larvae with the combination of pentamidine and ciprofloxacin resulted in enhanced efficacy compared with the monotherapies and significantly reduced the number of proliferating bacteria. Our measurement of efflux activity from cells revealed that pentamidine had a specific inhibitory effect on the MexCD-OprJ and MexEF-OprN efflux pumps. However, the efflux activity and membrane permeability assays revealed that pentamidine also disrupted the membrane of all cells. In conclusion, pentamidine does possess some efflux-pump inhibitory activity, in addition to a more general disruptive effect on membrane integrity that accounts for its ability to potentiate ciprofloxacin activity. Notably, the enhanced efficacy of combination therapy with pentamidine and ciprofloxacin versus MDR P. aeruginosa strains in vivo merits further investigation into its potential to treat infections via this pathogen in patients.
Discovery of Bactericidal Proteins from Staphylococcus Phage Stab21 Using a High-Throughput Screening Method
Antibiotics ( IF 0 ) Pub Date : 2023-07-21 , DOI: 10.3390/antibiotics12071213
EllisivNyhamar,PaigeWebber,OliviaLiong,ÖzgenurYilmaz,MariaPajunen,MikaelSkurnik,XingWan
In the escalating battle against antimicrobial resistance, there is an urgent need to discover and investigate new antibiotic strategies. Bacteriophages are untapped reservoirs of such potential antimicrobials. This study focused on Hypothetical Proteins of Unknown Function (HPUFs) from a Staphylococcus phage Stab21. We examined its HPUFs for bactericidal activity against E. coli using a Next Generation Sequencing (NGS)-based approach. Among the 96 HPUFs examined, 5 demonstrated cross-species toxicity towards E. coli, suggesting the presence of shared molecular targets between E. coli and S. aureus. One toxic antibacterial HPUF (toxHPUF) was found to share homology with a homing endonuclease. The implications of these findings are profound, particularly given the potential broad applicability of these bactericidal agents. This study confirms the efficacy of NGS in streamlining the screening process of toxHPUFs, contributes significantly to the ongoing exploration of phage biology, and offers promises in the search for potent antimicrobial agents.
Multi-Model Strategies for Prevention of Infection Caused by Certain Multi-Drug Resistant Organisms in A Rehabilitation Unit: A Semi-Experimental Study
Antibiotics ( IF 0 ) Pub Date : 2023-07-18 , DOI: 10.3390/antibiotics12071199
ShiyuLi,JiLin,SiyuanTao,LinwenGuo,WenzhiHuang,JingwenLi,ChunpingDu,ZhitingWang,LiwenLiu,YiChen,FuQiao
Objective: To assess the effectiveness of multi-model strategies on healthcare-associated infections (HAIs) caused by multi-drug resistant organisms (MDROs) in rehabilitation units. Methods: A semi-experimental study was conducted in a rehabilitation unit with 181 beds from January 2021 to December 2022 in a teaching hospital with 4300 beds in China. In 2021, many basic prevention and control measures were conducted routinely. Based on the basic measures, strengthening multi-model strategies for the prevention and control of MDROs was pursued year-round since 1 January 2022. Results: A total of 6206 patients were enrolled during the study period. The incidence density of HAIs caused by MDROs decreased from 1.22 (95% CI, 0.96~1.54) cases/1000 patient-days in the pre-intervention period to 0.70 (95% CI, 0.50~0.95) cases/1000 patient-days (p = 0.004). Similarly, the incidence of HAIs in the intervention period was 50.85% lower than that in the pre-intervention period (2.02 (95% CI, 1.50~2.72) vs. 4.11 (95% CI, 3.45–4.85) cases/100 patients, p < 0.001). The rate of MDROs isolated from the environment decreased by 30.00%, although the difference was not statistically significant (p = 0.259). Conclusion: Multi-model strategies can reduce the incidence of HAIs and HAIs caused by certain MDROs in the rehabilitation unit.
Moving toward Extensively Drug-Resistant: Four-Year Antimicrobial Resistance Trends of Acinetobacter baumannii from the Largest Department of Internal Medicine in Slovakia
Antibiotics ( IF 0 ) Pub Date : 2023-07-18 , DOI: 10.3390/antibiotics12071200
YasharJalali,AdrianaLiptakova,MonikaJalali,JurajPayer
A. baumannii imposes a great burden on medical systems worldwide. Surveillance of trends of antibiotic resistance provides a great deal of information needed for antimicrobial stewardship programmes nationwide. Clinical data from long-term, continuous surveillance on trends of antibiotic resistance of A. baumannii in Slovakia is missing. One hundred and forty-nine samples of A. baumannii were isolated over a period of four years. A panel of 19 antibiotics from seven antibiotic categories were tested for the bacterium’s susceptibility. Resistance results were evaluated, and the significance of patterns was estimated using simple linear regression analysis. All isolates were more than 85% resistant to at least 13 out of the 19 tested antibiotics. A significant rise in resistance was recorded for aminoglycosides and imipenem from 2019 to 2022. Colistin and ampicillin-sulbactam have been the only antibiotics maintaining more than 80% efficacy on the bacterium to date. A significant rise in extensively drug-resistant (XDR) strains among carbapenem-resistant (CR) isolates has been recorded. Multidrug-resistance (MDR) among all A. baumannii isolates and XDR among CR strains of the bacterium have risen significantly in the last four years.
Evaluation of the Antibacterial Activities of Mangrove Honeybee Propolis Extract and the Identification of Transpeptidase and Transglycosylase as Targets for New Antibiotics Using Molecular Docking
Antibiotics ( IF 0 ) Pub Date : 2023-07-17 , DOI: 10.3390/antibiotics12071197
MahaA.Alshiekheid
Developing new antibiotics is a critical area of research that grows as a result of the increasing problem of antibiotic resistance. Scientists search for new antibiotics by screening natural sources such as soil, plants, and marine environments. One of the iconic plants in the marine environment is the mangrove, which is a source of honeybee propolis. Propolis collected from the grey mangrove Avicennia marina on Tarout Island, the Eastern Province of Saudi Arabia, was used to evaluate antibacterial activities against three pathogenic bacteria: gram-negative Enterobacter cloacae (RCMB 001(1) ATCC® 23355TM), gram-positive methicillin-resistant Staphylococcus aureus (clinical isolate), and Streptococcus mutans Clark (RCMB 017(1) ATCC® 25175TM). The results indicate the effectiveness of the methanolic extract of such propolis. The chemical composition of this extract was analyzed using LC-MS, and four compounds were identified (alginic acid, carrageenan, fucoxanthin, cycloeudesmol). Their modes of action were evaluated against bacterial cell walls. Bacterial transpeptidase and transglycosylase on the surface are basic for cell divider amalgamation, and numerous antimicrobials have been created to target these compounds. Molecular docking was employed to predict the interactions of four compounds and S. aureus to predict interaction. Alginic acid was found to be the best interaction with a score of −7.44 Kcal/mol with distance ranges between 2.86 and 3.64 and RMSD refined below 2 Å. Carrageenan with −6.64 Kcal/mol and a distance of 3.05 and 2.87 came second. Then, fucoxanthin with −6.57 Kcal/mol and a distance of 1.4. Finally, cycloeudesmol with a score of −4.6 Kcal/mol and a distance of 2.87 showed the least activity. The first three compounds interacted effectively and could form very promising chemicals that could be used one day against pathogenic bacteria in the future.
Drug Utilization Evaluation and Impact of Pharmacist Interventions on Optimization of Piperacillin/Tazobactam Use: A Retrospective Analysis and Prospective Audit
Antibiotics ( IF 0 ) Pub Date : 2023-07-15 , DOI: 10.3390/antibiotics12071192
SaveraArain,FahadKhalawi,SainulAbideenParakkal,HassanS.AlHamad,ShabeerAliThorakkattil,FaisalFahadJ.Alghashmari,BaderAlHarbi,NujudBakhashwain,WeaamMustafaAlzawad,AliAlHomoud
(1) Background: Piperacillin/tazobactam is a broad-spectrum antimicrobial encompassing most Gram-positive and Gram-negative aerobic and anaerobic bacteria. The inappropriate use of such broad-spectrum antibiotics is an important contributor to the rising rates of antimicrobial drug resistance worldwide. Drug utilization evaluation studies and pharmacists’ interventions are vital to assess, develop, and promote the rational use of antibiotics. This drug utilization study aimed to evaluate the current utilization practice of piperacillin/tazobactam in a hospital setting and assess the impact of pharmacist intervention in improving its appropriate use. (2) Methodology: In this study, we used a retrospective cohort and a prospective cohort, a cross-sectional, observational method. It included a retrospective (Cycle A/pre-intervention-CycA) phase followed by an educational interventional phase conducted by the pharmacists. During the 2 months of educational intervention, pharmacists used several methods, including workshops, lectures, oral presentations, and the development and reinforcement of clinical pathways to promote the judicious use of piperacillin/tazobactam. This was followed by a prospective (Cycle B/post-intervention-CycB) phase to improve piperacillin/tazobactam usage appropriateness. The appropriateness criteria for this drug utilization evaluation were established based on antimicrobial guidelines, the published literature, the institutional antibiogram, consultation from the antimicrobial stewardship committee, and the product monograph (Tazocin). The appropriateness of CycA and CycB patients was compared using the measurable elements, including indication and dose based on renal function, timely order for cultures, de-escalation, and use of extended infusion protocol. (3) Results: The study population comprised 100 patients in both CycA and CycB. The mean age of the patients was 66.28 ± 16.15 and 67.35 ± 17.98, and the ratios of men to women were found to be 49:51 and 61:39 in CycA and CycB, respectively. It was observed that inappropriate usage was high in CycA patients, and the appropriateness was improved in CycB patients. A total of 31% of inappropriate empirical broad-spectrum use was found in CycA, and it was reduced to 12% in CycB patients. The transition of appropriateness was observed in all measurable criteria, which includes the optimized dose according to the renal function (CycA = 49% to CycB = 94%), timely bacterial culture orders (CycA = 47% to CycB = 74%), prompt de-escalation (CycA = 31% to CycB = 53%), and adherence to extended infusion institutional guidelines (CycA = 34% to CycB = 86%). (4) Conclusions: The study highlighted important aspects of inappropriate piperacillin/tazobactam use. This can be considerably improved by proper education and timely interventions based on the pharmacists’ vigilant approach. The study results emphasized the need for surveillance of piperacillin/tazobactam usage by conducting similar drug utilization evaluations and practice to improve quality and safety in healthcare organizations globally.
Occurrence of Antimicrobial Resistance in Canine and Feline Bacterial Pathogens in Germany under the Impact of the TÄHAV Amendment in 2018
Antibiotics ( IF 0 ) Pub Date : 2023-07-15 , DOI: 10.3390/antibiotics12071193
MarianneMoerer,AntinaLübke-Becker,AstridBethe,RoswithaMerle,WolfgangBäumer
The occurrence of antimicrobial resistance due to the use of antimicrobials is considered to be a main cause for treatment failure of bacterial infections in humans and animals. The right of German veterinarians to use and prescribe medications such as antimicrobials is regulated by the Regulation of Veterinary Pharmacies (TÄHAV). The aim of this study was to investigate the impact of the second amendment to the TÄHAV in 2018 on the occurrence of antimicrobial resistance in selected bacterial pathogens isolated from dogs and cats in Germany. For this purpose, we analyzed antimicrobial susceptibility data from 38 German small animal practices gathered between 2015 and 2021 in cooperation with Laboklin (Labor für klinische Diagnostik GmbH & Co.KG, Bad Kissingen, Germany). Annual cumulative susceptibility data of eight bacterial species were analyzed and compared. The mean value of resistant isolates was determined for each year and supplemented by 95% confidence intervals. Encouraged by the amendment, an increase in sample submissions was observed in Germany. The highest resistance rates to the analyzed substances penicillin G, ampicillin, amoxicillin-clavulanic acid, cefovecin, and enrofloxacin were found for Staphylococcus pseudintermedius (S. pseudintermedius), S. aureus, and Escherichia coli (E. coli). In contrast, resistance rates were low for Pasteurella multocida (P. multocida) and β-hemolytic streptococci. Significant resistance trends (p < 0.05) assumed as influenced by the TÄHAV amendment could be the significant decreases in resistance rates of S. pseudintermedius against penicillin G to 67% (n = 322/479), and ampicillin to 63% (n = 286/453), as well as S. felis against amoxicillin-clavulanic acid and cefovecin to 2% (n = 2/109), furthermore, the reduction in the occurrence of resistance of S. aureus against enrofloxacin to 4% (n = 3/76) in 2021. Moreover, for all species, the efficacy against the analyzed substances was maintained over the study period.
A Study Review of the Appropriateness of Oral Antibiotic Discharge Prescriptions in the Emergency Department at a Rural Hospital in Mississippi, USA
Antibiotics ( IF 0 ) Pub Date : 2023-07-14 , DOI: 10.3390/antibiotics12071186
GiangLe,MadalynIvy,SharonDickey,RonWelch,DanielleStallings
Antimicrobial therapy in emergency departments (EDs) is usually empiric in nature. Due to workload and a goal to reduce patient wait times, providers often make rapid decisions regarding antibiotic prescriptions for discharge. A review of current empiric prescribing practices would determine the appropriateness of oral antibiotic discharge prescriptions from EDs. A single-center retrospective electronic health record review of all adult patients with an ED visit from 1 June 2019, to 30 June 2021 who received at least one oral antibiotic prescription at discharge from Baptist Memorial Hospital-Golden Triangle was conducted. The primary outcome was the assessment of appropriate antibiotic discharge prescriptions. The parameters for appropriateness included empiric drug selection, dosage, frequency, duration, and subsequent cultures and sensitivities. Of the 18,289 identified records, 421 patients were randomly sampled with 400 patients included in the final analysis. Of these, 190 (47.8%) discharge oral antibiotic prescriptions were assessed as appropriate and 209 (52.3%) discharge oral antibiotic prescriptions were assessed as inappropriate based on the guideline recommendations. With approximately half of the patients receiving discharge antibiotics that did not fully follow the guideline recommendations, there is a need for provider education, pharmacist intervention, and antimicrobial stewardship programs focusing on this practice.
A Review on Enterocin DD14, the Leaderless Two-Peptide Bacteriocin with Multiple Biological Functions and Unusual Transport Pathway
Antibiotics ( IF 0 ) Pub Date : 2023-07-14 , DOI: 10.3390/antibiotics12071188
RabiaLadjouzi,ElodieDussert,RadjaTeiar,YanathBelguesmia,DjamelDrider
Enterocin DD14 (EntDD14) is a two-peptide leaderless bacteriocin (LLB) produced by Enterococcus faecalis 14, a human strain isolated from meconium. Studies performed on EntDD14 enabled it to show its activity against Gram-positive bacteria such as Listeria monocytogenes, Clostridium perfringens, Enterococcus faecalis, and Staphylococcus aureus. EntDD14 was also shown to potentiate the activity of different antibiotics such as erythromycin, kanamycin, and methicillin when assessed against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo in the NMRI-F holoxenic mouse model. Additionally, EntDD14 has an antiviral activity and decreased the secretion of pro-inflammatory IL-6 and IL-8 in inflamed human intestinal Caco-2 cells. The genome of E. faecalis 14 was sequenced and annotated. Molecular tools such as Bagel4 software enabled us to locate a 6.7kb-EntDD14 cluster. Transport of EntDD14 outside of the cytoplasm was shown to be performed synergistically by a channel composed of two pleckstrin-homology-domain-containing proteins, namely DdE/DdF and the ABC transporter DdGHIJ. This latter could also protect the bacteriocinogenic strain against extracellular EntDD14. Here, we focus on academic data and potential therapeutic issues of EntDD14, as a model of two-peptide LLB.
In Vitro Antifungal Activity of Three Synthetic Peptides against Candida auris and Other Candida Species of Medical Importance
Antibiotics ( IF 0 ) Pub Date : 2023-07-26 , DOI: 10.3390/antibiotics12081234
RicharTorres,AdrianaBarreto-Santamaría,GabrielaArévalo-Pinzón,CarolinaFiracative,BeatrizL.Gómez,PatriciaEscandón,ManuelAlfonsoPatarroyo,JuliánE.Muñoz
Candidiasis is an opportunistic infection affecting immunosuppressed and hospitalized patients, with mortality rates approaching 40% in Colombia. The growing pharmacological resistance of Candida species and the emergence of multidrug-resistant Candida auris are major public health problems. Therefore, different antimicrobial peptides (AMPs) are being investigated as therapeutic alternatives to control candidiasis effectively and safely. This work aimed to evaluate the in vitro antifungal activity of three synthetic AMPs, PNR20, PNR20-1, and 35409, against ATCC reference strains of Candida albicans, Candida glabrata, Candida parapsilosis, Candida krusei, and Candida tropicalis, and clinical isolates of C. auris. Antifungal susceptibility testing, determined by broth microdilution, showed that the AMPs have antifungal activity against planktonic cells of all Candida species evaluated. In C. auris and C. albicans, the peptides had an effect on biofilm formation and cell viability, as determined by the XTT assay and flow cytometry, respectively. Also, morphological alterations in the membrane and at the intracellular level of these species were induced by the peptides, as observed by transmission electron microscopy. In vitro, the AMPs had no cytotoxicity against L929 murine fibroblasts. Our results showed that the evaluated AMPs are potential therapeutic alternatives against the most important Candida species in Colombia and the world.
Two-Stage Revision Arthroplasty for Resistant Gram-Positive Periprosthetic Joint Infections Using an Oral Linezolid-Based Antibiotic Regime
Antibiotics ( IF 0 ) Pub Date : 2023-07-26 , DOI: 10.3390/antibiotics12081235
LarsGründer,SebastianBockholt,GeorgGosheger,MartinSchulze,JanSchwarze,JanPützler,BurkhardMoellenbeck,ChristophTheil
Background: Increasing antibiotic resistance has been reported as an issue in the systemic treatment of periprosthetic joint infection (PJI). Linezolid offers the advantages of high oral bioavailability and little resistance; however, efficacy in the treatment of PJI varies considerably, and studies reporting consistent surgical treatment are scarce. Methods: This is a retrospective, single-center analysis of two-stage revisions performed between 2008 and 2017. We identified 111 patients who met the inclusion criteria. Oral linezolid was given for 28 days following 14 days of intravenous tailored antibiotics in resistant gram-positive PJI. A total of 64% of the patients had methicillin-resistant coagulase-negative staphylococci. The median follow-up was 43 (interquartile range (IQR) 30–57) months. Results: 22% (24/111) of the patients underwent surgery for subsequent infection. The 5-year infection-free survival probability was 77% (95% confidence interval (CI) 69–85). A total of 5% of the patients (6/111) had the same organism at the time of reinfection. The patients with infections caused by other organisms than Coagulase-negative staphylococci tended to have a worse reinfection-free survivorship at five years (70% vs. 81%, p = 0.09). Furthermore, the patients with obesity tended to have reduced reinfection-free survivorship at five years (69% vs. 84%, p = 0.08). Overall, 5% (6/111) of the patients had blood count abnormalities with no treatment discontinuations. Conclusion: Two-stage revision arthroplasty with systemic oral linezolid treatment for resistant gram-positive PJI results in an infection control of 77% at the mid-term.
Engineering 3D-Printed Advanced Healthcare Materials for Periprosthetic Joint Infections
Antibiotics ( IF 0 ) Pub Date : 2023-07-25 , DOI: 10.3390/antibiotics12081229
IvánYuste,FrancisC.Luciano,BrayanJ.Anaya,PabloSanz-Ruiz,AlmudenaRibed-Sánchez,ElenaGonzález-Burgos,DoloresR.Serrano
The use of additive manufacturing or 3D printing in biomedicine has experienced fast growth in the last few years, becoming a promising tool in pharmaceutical development and manufacturing, especially in parenteral formulations and implantable drug delivery systems (IDDSs). Periprosthetic joint infections (PJIs) are a common complication in arthroplasties, with a prevalence of over 4%. There is still no treatment that fully covers the need for preventing and treating biofilm formation. However, 3D printing plays a major role in the development of novel therapies for PJIs. This review will provide a deep understanding of the different approaches based on 3D-printing techniques for the current management and prophylaxis of PJIs. The two main strategies are focused on IDDSs that are loaded or coated with antimicrobials, commonly in combination with bone regeneration agents and 3D-printed orthopedic implants with modified surfaces and antimicrobial properties. The wide variety of printing methods and materials have allowed for the manufacture of IDDSs that are perfectly adjusted to patients’ physiognomy, with different drug release profiles, geometries, and inner and outer architectures, and are fully individualized, targeting specific pathogens. Although these novel treatments are demonstrating promising results, in vivo studies and clinical trials are required for their translation from the bench to the market.
Enterococcus hirae Mitral Valve Infectious Endocarditis: A Case Report and Review of the Literature
Antibiotics ( IF 0 ) Pub Date : 2023-07-25 , DOI: 10.3390/antibiotics12081232
RobertaGaudiano,MarcelloTrizzino,SalvatoreTorre,RobertaVirruso,FabioFiorino,VincenzoArgano,AntonioCascio
Enterococcus hirae is a rare pathogen in human infections, although its incidence may be underestimated due to its difficult isolation. We describe the first known case of E. hirae infective endocarditis (IE), which involves the mitral valve alone, and the seventh E. hirae IE worldwide. Case presentation: a 62-year-old male was admitted to our department with a five-month history of intermittent fever without responding to antibiotic treatment. His medical history included mitral valve prolapse, recent pleurisy, and lumbar epidural steroid injections due to lumbar degenerative disc disease. Pre-admission transesophageal echocardiography (TEE) showed mitral valve vegetation, and Enterococcus faecium was isolated on blood cultures by MALDI-TOF VITEK MS. During hospitalization, intravenous (IV) therapy with ampicillin and ceftriaxone was initiated, and E. hirae was identified by MALDI-TOF Bruker Biotyper on three blood culture sets. A second TEE revealed mitral valve regurgitation, which worsened due to infection progression. The patient underwent mitral valve replacement with a bioprosthetic valve and had an uncomplicated postoperative course; he was discharged after six weeks of IV ampicillin and ceftriaxone treatment.
Prevalence of Carbapenemases in Carbapenem-Resistant Acinetobacter baumannii Isolates from the Kingdom of Bahrain
Antibiotics ( IF 0 ) Pub Date : 2023-07-17 , DOI: 10.3390/antibiotics12071198
NoufAl-Rashed,KhalidM.Bindayna,MohammadShahid,NerminKamalSaeed,AbdullahDarwish,RonniMolJoji,AliAl-Mahmeed
Background: Acinetobacter baumannii is regarded as a significant cause of death in hospitals. The WHO recently added carbapenem-resistant Acinetobacter baumannii (CRAB) to its global pathogen priority list. There is a dearth of information on CRAB from our region. Methods: Fifty CRAB isolates were collected from four main hospitals in Bahrain for this study. Bacterial identification and antibiotic susceptibility tests were carried out using the BD PhoenixTM and VITEK-2 compact, respectively. Using conventional PCR, these isolates were further screened for carbapenem resistance markers (blaOXA-51, blaOXA-23, blaOXA-24, blaOXA-40, blaIMP, blaNDM, blaVIM, and blaKPC). Results: All of the isolates were resistant to imipenem (100%), meropenem (98%), and cephalosporins (96–98%), followed by other commonly used antibiotics. All these isolates were least resistant to gentamicin (64%). The detection of resistance determinants showed that the majority harbored blaOXA-51 (100%) and blaIMP (94%), followed by blaOXA-23 (82%), blaOXA-24 (46%), blaOXA-40 (14%), blaNDM (6%), blaVIM (2%), and blaKPC (2%). Conclusion: The study isolates showed a high level of antibiotic resistance. Class D carbapenemases were more prevalent in our CRAB isolate collection. The resistance genes were found in various combinations. This study emphasizes the importance of strengthening surveillance and stringent infection control measures in clinical settings to prevent the emergence and further spread of such isolates.
In Vitro Activity of Cefiderocol against a Global Collection of Carbapenem-Resistant Acinetobacter baumannii Isolates
Antibiotics ( IF 0 ) Pub Date : 2023-07-11 , DOI: 10.3390/antibiotics12071172
HaraldSeifert,CarinaMüller,DanutaStefanik,PaulG.Higgins,EstherWohlfarth,MichaelKresken
Background: Cefiderocol is a novel siderophore cephalosporin with potent activity against multi-drug-resistant Gram-negative pathogens including carbapenem-resistant Acinetobacter baumannii (CRAB). Methods: The susceptibility of 313 non-duplicate CRAB isolates with defined carbapenem resistance mechanisms from a global collection to cefiderocol, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, ciprofloxacin, colistin, imipenem/relebactam, meropenem, meropenem/vaborbactam, minocycline, and piperacillin/tazobactam was determined using the broth microdilution method. Isolates were obtained from various body sites from patients in 47 countries in five world regions between 2012 and 2016. The identification of carbapenem resistance mechanisms and assignment to A. baumannii international clonal lineages were based on whole genome sequencing. Results: Cefiderocol showed greater activity than comparator antimicrobials of the β-lactam class, including novel β-lactams combined with β-lactamase inhibitors, ciprofloxacin, and minocycline. Cefiderocol MIC50 and MIC90 values were 0.5 mg/L and 4 mg/L, respectively, while colistin had comparable activity with a higher MIC50 at 1 mg/L and a lower MIC90 value of 2 mg/L. Many isolates with elevated cefiderocol MICs ≥ 4 mg/L represented A. baumannii international clone (IC) 1 and harbored a metallo-β-lactamase. Conclusions: While cefiderocol is a useful addition to the limited armamentarium of drugs targeting this problematic pathogen, a considerable part of CRAB isolates had elevated MIC values in a range of 4 -> 32 mg/L, including all isolates with a metallo-β-lactamase.
Screening for Antimicrobial Resistance and Genes of Exotoxins in Pseudomonas aeruginosa Isolates from Infected Dogs and Cats in Poland
Antibiotics ( IF 0 ) Pub Date : 2023-07-24 , DOI: 10.3390/antibiotics12071226
DariaPłókarz,KarolinaBierowiec,KrzysztofRypuła
Pseudomonas aeruginosa has assumed an increasingly prominent role as the aetiological agent in serious hard-to-treat infections in animals and humans. In this study, 271 P. aeruginosa strains collected from dogs and cats were investigated. The aim of the research was to screen these P. aeruginosa strains for antibiotic resistance and the presence of selected virulence factor genes. Antibiotic resistance was determined using the Kirby–Bauer method, while virulence genes were detected by polymerase chain reaction (PCR). The most frequently detected resistance was to fluoroquinolones, ranging in prevalence from 17.3% for ciprofloxacin up to 83% for enrofloxacin. The resistance to carbapenems was 14% and 4.8% for imipenem and meropenem, respectively. Almost all P. aeruginosa strains harboured the exoT (97.8%) and lasB (93.4%) genes, while the lowest prevalence was found for exoU (17.3%) and plcH (17.3%). P. aeruginosa strains isolated from dogs that harboured the toxA gene were more frequently resistant to ceftazidime (p = 0.012), while the presence of the exoU gene was found to be connected with resistance to marbofloxacin (p = 0.025) and amikacin (p = 0.056). In strains originating from cats, only the connection between the presence of the exoU gene and resistance to enrofloxacin (p = 0.054) was observed. The confirmation of associations between virulence-factor-encoding genes and antibiotic resistance indicates that problems of antibiotic resistance may not only cause complications at the level of antibiotic dosage but also lead to changes in the virulence of the bacteria; thus, further studies in this area are required.
Development of a Polymicrobial Checkerboard Assay as a Tool for Determining Combinatorial Antibiotic Effectiveness in Polymicrobial Communities
Antibiotics ( IF 0 ) Pub Date : 2023-07-20 , DOI: 10.3390/antibiotics12071207
CarolineBlack,HafijAlMahmud,VictoriaHowle,SabrinaWilson,AllieC.Smith,CatherineA.Wakeman
The checkerboard assay is a well-established tool used to determine the antimicrobial effects of two compounds in combination. Usually, data collected from the checkerboard assay use visible turbidity and optical density as a readout. While helpful in traditional checkerboard assays, these measurements become less useful in a polymicrobial context as they do not enable assessment of the drug effects on the individual members of the community. The methodology described herein allows for the determination of cell viability through selective and differential plating of each individual species in a community while retaining much of the high-throughput nature of a turbidity-based analysis and requiring no specialized equipment. This methodology further improves turbidity-based measurements by providing a distinction between bacteriostatic versus bactericidal concentrations of antibiotics. Herein, we use this method to demonstrate that the clinically used antibiotic combination of ceftazidime and gentamicin works synergistically against Pseudomonas aeruginosa in monoculture but antagonistically in a polymicrobial culture also containing Acinetobacter baumannii, Staphylococcus aureus, and Enterococcus faecalis, highlighting the fundamental importance of this methodology in improving clinical practices. We propose that this method could be implemented in clinical microbiology laboratories with minimal impact on the overall time for diagnosis.
Evaluation of the BD Phoenix CPO Detect Panel for Detection and Classification of Carbapenemase Producing Enterobacterales
Antibiotics ( IF 0 ) Pub Date : 2023-07-21 , DOI: 10.3390/antibiotics12071215
HarshadLade,SeriJeong,KibumJeon,Han-SungKim,HyunSooKim,WonkeunSong,Jae-SeokKim
Carbapenem-resistant Enterobacterales (CRE) pose a serious public health threat due to their resistance to most antibiotics. Rapid and correct detection of carbapenemase producing organisms (CPOs) can help inform clinician decision making on antibiotic therapy. The BD Phoenix™ CPO detect panel, as part of antimicrobial susceptibility testing (AST), detects carbapenemase activity (P/N) and categorizes CPOs according to Ambler classes. We evaluated a CPO detect panel against 109 carbapenemase producing Enterobacterales (CPE) clinical isolates from Korea. The panel correctly detected carbapenemases production in 98.2% (n = 107/109) isolates and identified 78.8% (n = 26/33) class A, 65.9% (n = 29/44) class B, and 56.3% (n = 18/32) class D carbapenemase producers as harboring their corresponding Ambler classes. Specifically, the panel correctly classified 81.3% (n = 13/16) of K. pneumoniae KPC isolates to class A. However, the panel failed to classify 40.0% (n = 4/10) IMP and 63.6% (n = 7/11) VIM isolates to class B. Despite 27.5% (n = 30/109) CPE not being assigned Ambler classes, all of them tested carbapenemase positive. Our results demonstrate that the CPO detect panel is a sensitive test for detecting CPE and classifying KPC as class A, helping with antibiotics selection, but one-third of CPE remained unclassified for Ambler classes.
Native-Valve Aspergillus Endocarditis: Case Report and Literature Review
Antibiotics ( IF 0 ) Pub Date : 2023-07-14 , DOI: 10.3390/antibiotics12071190
ClaudioCaroselli,LorenzoRobertoSuardi,LauraBesola,AlessandroFiocco,AndreaColli,MarcoFalcone
Aspergillus endocarditis represents the second etiological cause of prosthetic endocarditis following Candida spp. On the other hand, native-valve endocarditis due to Aspergillus are anecdotally reported with increasing numbers in the last decade due to new diagnostic technologies such as polymerase chain reaction (PCR) on samples like valve tissue or entire blood. We performed a review of the literature presenting one case report observed at Pisa University Hospital. Seventy-four case reports have been included in a period between 1950–2022. Immunocompromised status (patients with solid tumor/oncohematological cancer or transplanted patients) was confirmed to be the main risk factor for this rare opportunistic infection with a high rate of metastatic infection (above all, central nervous system) and mortality. Diagnosis relies on serum galactomannan and culture with PCR on valve tissue or whole blood. Cardiac surgery was revealed to be a life-saving priority as well as appropriate antifungal therapy including b-liposomal amphotericin or new triazoles (isavuconazole). The endocarditis team, facing negative blood culture endocarditis affecting an immunocompromised patient, should investigate this difficult-to-treat pathogen.
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自引率 H-index SCI收录状况 PubMed Central (PML)
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